In ion cyclotron resonance mass spectrometers (ICR-MS), the mass-to-charge ratios m/z of ions are measured by their cyclotron motions in a homogeneous magnetic field with high field strength. The magnetic field is usually generated by superconductive magnetic coils cooled with liquid helium. Nowadays they provide usable cell diameters of around 6 to 12 centimeters at magnetic field strengths of 7 to 12 Tesla.
The orbital frequency of the ions (ion cyclotron frequency) is measured in ICR measuring cells located within the homogeneous part of the magnetic field. The cylindrical ICR measuring cell normally comprises four longitudinal electrodes in the shape of a fourfold slit cylinder parallel to the magnetic field lines, surrounding the measuring cell. Usually, two of these electrodes are used to bring ions, which are introduced close to the axis, into their cyclotron orbits (into their cyclotron motion), ions with the same mass-to-charge ratio being excited as in-phase as possible in order to obtain a synchronously orbiting clouds of ions. The other two electrodes serve to measure the orbiting of the ion clouds by their image currents, which are induced in the electrodes as the ion clouds fly past. The term “image currents” is normally used even though it is actually the induced “image voltages” which are measured. The process of introducing the ions into the measuring cell, ion excitation and ion detection are carried out in successive phases of the method.
Since the mass-to-charge ratio of the ions (referred to below simply as “specific mass”, and sometimes simply as “mass”) is unknown before the measurement, the ions are excited by a mixture of all possible excitation frequencies. The mixture can be a temporal mixture in which the frequencies increase with time (called a “chirp”), or it can be a synchronous, computer-calculated mixture of all frequencies (a “sync pulse”). By specially selecting the phases, the synchronous mixture of the frequencies can be formed so that the amplitudes of the mixture remain restricted to the dynamic range of the digital-to-analog converter, which produces the time sequence of analog voltages forming the mixture of frequencies.
The image currents induced by the ions in the detection electrodes are amplified, digitized and analyzed by Fourier analysis for the orbital frequencies of the different ion clouds with different specific masses present therein. The Fourier analysis transforms the original measurements of the image current values in the “time domain” into frequency values in a “frequency domain”, hence the term Fourier transform mass spectrometry (FTMS). The specific masses of the ions and their intensities are then determined from the frequencies of the signals, which can be recognized as peaks in the frequency domain. Owing to the extraordinarily high constancy of the magnetic fields used, and the high accuracy for frequency measurements, it is possible to achieve an extraordinarily accurate mass determination. At present, Fourier transform mass spectrometry is the most accurate of all types of mass spectrometry. Ultimately, the accuracy of mass determination depends only on the number of ion orbits which can be detected by the measurement.
The longitudinal electrodes usually form a measuring cell with a square or circular cross-section. The cylindrical measuring cell usually contains four cylinder segments as longitudinal electrodes. Cylindrical measuring cells are the ones most commonly used because they offer the best utilization of the magnetic field, although the image currents of focused clouds of ions with the same mass (image voltages) come close to a rectangular curve. However, the smearing of the ion clouds, which is always observed, leads to image current signals for each ionic species which have a rather more sinusoidal shape.
Since the ions can move freely in the direction of the magnetic field lines, the ions, which each possess velocity components in the direction of the magnetic field from the filling process, must be prevented from leaving the measuring cell. To prevent ion losses, the measuring cells are therefore equipped at both ends with electrodes, known as “trapping electrodes”. These are supplied with ion-repelling DC potentials in order to keep the ions in the measuring cell. There are widely differing configurations for this electrode pair; the simplest ones comprise planar electrodes with a central aperture. The aperture serves to introduce the ions into the measuring cell.
The ion-repelling potentials form a potential sink in the interior of the measuring cell, with a parabolic potential profile along the axis of the measuring cell. The potential profile is only slightly dependent on the configuration of these electrodes. The potential profile along the axis is at its minimum at precisely the mid-point of the measuring cell if the ion-repelling potentials across both electrodes have the same value. The ions introduced will therefore execute oscillations in this potential well in the axial direction—so-called trapping oscillations—because they posses kinetic energy in the axial direction left over from their introduction into the cell. The amplitude of these trapping oscillations depends on their kinetic energy.
The electric field outside the axis of the measuring cell is more complicated. Owing to the potentials of the trapping electrodes at the ends and the longitudinal electrodes, the electric field inevitably contains components in the radial direction of the cell which generate a second type of ion motion: the magnetron circular motion. The magnetron gyroscopic motion is also a circular motion about the axis of the measuring cell, but much slower than the cyclotron circular motion. The additional magnetron circular motion causes the mid-points of the cyclotron circular motions to rotate around the axis of the measuring cell at the frequency of the magnetron motion, with the result that the trajectory of the ions describes a cycloidal motion.
The superimposition of magnetron and cyclotron circular motion is an undesirable phenomenon which leads to a frequency shift in the cyclotron frequency. Furthermore, it leads to a reduction in the usable volume of the measuring cell. The measured frequency ωm (the “reduced cyclotron frequency”) amounts to
            ω      m        =                            ω          c                2            +                                                  ω              c              2                        4                    -                                    ω              t              2                        2                                ,where ωc is the undisturbed cyclotron frequency, and ωt the frequency of the trapping oscillation. The trapping oscillation determines the effect of the magnetron circular motion on the cyclotron circular motion. A measuring cell without magnetron circular motion would be very advantageous because the cyclotron frequency could be directly measured and no corrections would have to be applied.
In principle, it is possible to switch the type of motion of the orbiting ions to and fro between a pure magnetron motion and a pure cyclotron motion by supplying and removing energy to the different types of motion by means of quadrupolar excitation, which requires four excitation electrodes, with RF pulses that have a mixture of frequencies. It is thus possible to generate a pure cyclotron motion if the irradiation is ended in the correct phase. But a further dipolar excitation of the cyclotron motion immediately generates a magnetron motion again.
The vacuum in the measuring cell must be as good as possible because, during measurement of the image currents, the ions must not collide with molecules of residual gas. Each collision of an ion with a molecule of residual gas brings the ion out of the orbiting phase of the other ions with the same specific mass. The loss of phase homogeneity leads to a reduction in the image currents and to a continuous decrease in the signal-to-noise-ratio, which reduces the usable measuring period. The measurement period should amount to at least a few hundred milliseconds, ideally a few seconds. This requires a ultrahigh vacuum in the region of 10−7 to 10−9 Pascal.
Apart from the vacuum, the space charge in the ion cloud can also adversely affect the measurement. The Coulomb repulsion between the ions themselves and, above all, the elastic reflection of the ions moving in the cloud lead to a large number of disturbances, which also result in an expansion of the cloud. In present-day instruments, the space charge, alongside the effects of pressure, represents the greatest limitation on achieving high mass accuracy.
For higher specific ion masses, the decrease in the cyclotron orbital frequency of the ions is inversely proportional to the mass. The resolution, however, is proportional to the number of measured orbits; it is therefore lower for ions of high specific masses than for those of low specific masses, although it is of particular interest for high ion masses to have a high resolution and, correspondingly, a high mass accuracy. Ever since the introduction of ion cyclotron mass spectrometers, attempts have repeatedly been made to increase the resolution for higher specific ion masses as well, by using a larger number of detection electrodes to multiply the frequency of the image currents in relation to the cyclotron frequency. If a total of 16 detection electrodes are used instead of two, then the two phases of the image current are each measured eight times, and the measured frequency increases by a factor of eight. It is to be expected that resolution and mass accuracy are also increased by a factor of eight if measured over the same measuring time. This requires that the diameter of the orbiting ion cloud be not much larger than the width of the detection electrodes. The use of a large number of detection electrodes is therefore precluded by the continuous increase in volume of the ion clouds and especially their magnetron motion.
Unfortunately, these experiments have had such limited success that they have regularly been abandoned. The reasons for the moderate success have been briefly mentioned above, but they have basically not been fully explained. It can be assumed that the ion clouds do not hold together well enough and that, for this reason, they cannot be brought close enough to the detection electrodes. Narrow electrodes require that the ion clouds are brought very close, as otherwise it is scarcely possible to induce the full image currents.
Recently, measuring cells for ion cyclotron resonance mass spectrometry have been described in which practically no magnetron circular motion can develop. (E. Nikolaev, Lecture at the International Mass Spectrometry Conference (IMSC) in Edinburgh, September 2003). In this case, the trapping electrodes are replaced with fine bipolar grid structures, to which an RF voltage is applied and which thus reflect ions of both polarities because of their pseudopotential if the ions possess a specific mass above a mass threshold. The mass threshold can be adjusted by the RF voltage. Grid and punctiform electrode structures of this type have been proposed in U.S. Pat. No. 5,572,035 (J. Franzen). The pseudopotential has a very short range of the order of magnitude of the separations between these structural elements. The reflection resembles a hard reflection on a matt disk, the scattering effect of the matt disk decreasing as the angle of incidence flattens out.
An RF field around the tip of a wire decreases outward in proportion to 1/r2; the RF field of a long wire decreases at 1/r, where r is the distance from the tip or axis of the wire. Both RF fields repel both positive and negative particles. The particle oscillates in the RF field. Regardless of its charge, it experiences the strongest repelling force when it is located near to the wire, i.e. at the point where the field strength is highest. It experiences the strongest attractive force when it is at the furthermost point, i.e. at the point on its oscillation path where the field strength is lowest. Integration over time results in a repulsion. This time-integrated repulsion potential is known as “pseudopotential”, sometimes also as “effective potential” or “quasi-potential”. The pseudopotential is proportional to the square of the RF field, i.e. it decreases outward at 1/r2 in the case of a long wire. Moreover, the pseudopotential is inversely proportional to the specific mass m/z of the particles and to the square ω2 of the RF frequency ω. There is a lower mass threshold for the reflection of the particles.
A relatively easily manufactured surface, made of a grid of parallel wires, where the grid wires are connected alternately to the phases of an RF voltage, has a very short-range pseudopotential. The RF field of a grid with wires of 0.1 millimeter, one millimeter apart, falls to 5% in one millimeter, to 0.2% in two millimeters and to 0.009% in three millimeters. The pseudopotential, which is proportional to the square of this field, falls off much more quickly: At a distance of one millimeter, there is a pseudopotential of only 0.25% of the pseudopotential on the surface of the wire.
In measuring cells with trapping electrodes which have this type of pseudopotential, the ions are stored as fine ion clouds in the shape of a string each with no magnetron motion. Owing to their kinetic energy, the ions can move to and fro in the axial direction in the ion string; they undergo hard reflection at each of the trapping electrodes. The slightly scattering reflections lead to minuscule helical motions of the ions. The ion string as a whole can now be excited via suitable chirp or sync pulses so that they perform cyclotron motions. In the orbiting ion string, the scattering effect of the reflections also decreases, so that the diameter of the ion string only increases very slowly. These long ion strings can consist of significantly more ions than previous measuring cells without the space charge adversely affecting the cyclotron circular motion. Furthermore, the space charge only allows the diameter of the ion string to increase very slowly.
It is possible to arrange the grids of the trapping electrodes so that the crosstalk of the RF voltage at the grid wires onto the image-current measuring electrodes is very low. Unfortunately, it cannot be eliminated completely, however. The frequency of the trapping RF must therefore be set in a range outside that of the induced cyclotron frequencies of the ions, and attempts must be made to remove the induced voltage residues with electrical filter methods. However, since the RF voltages of the trapping electrodes lie between 10 and 100 volts, but the image voltages are only in the range of microvolts or less, this filtering is difficult. Moreover, it appears that overtones, ripple voltages and interferences repeatedly result in frequencies in the range of the image currents, making measurement difficult.